1-(4-Bromo-thiazol-2-yl)-ethanol synthesis

Yield:1370356-21-0 65%

Reaction Conditions:

Stage #1: 2,4-dibromo-1,3-thiazolewith TurboGrignard in tetrahydrofuran at -78; for 0.25 h;Inert atmosphere;
Stage #2: acetaldehyde in tetrahydrofuran at -78 - 0; for 1.66667 h;Inert atmosphere;
Stage #3: with water;ammonium chloride in tetrahydrofuran at 0;Inert atmosphere;

Steps:

4.3.1. Procedure A for the preparation of racemic alcohols rac-2a-h and 2-formylthiazoles 3a,b

General procedure: The reaction was carried out in a sealed tube under N₂ using THF (4 mL) as the solvent. To the solution of tert-butyl 2-bromothiazole-4-carboxylate 1a (0.397 mmol), ⁱPrMgCl·LiCl (1.3 M, 0.52 mmol) was added dropwise at -78 °C. After 15 min the corresponding aldehyde (0.79-0.99 mmol) or N-formyl-morpholine (in the case of 2-formylthiazoles 3a-b) was added dropwise under stirring and the reaction mixture was stirred at -78 °C for 10 min, then 1.5 h at 0 °C. Saturated aqueous NH₄Cl was added and the aqueous layer was extracted with Et₂O (3 × 10 mL). The combined organic layers were washed with 5% aqueous HCl (10 mL), brine (10 mL), dried over MgSO₄ and concentrated in vacuo. The crude product was purified by flash column chromatography on silica gel using a mixture of EtOAc:P (petroleum ether) as eluent (see below) to give tert-butyl 2-(1-hydroxymethyl)thiazole-4-carboxylate derivatives rac-2a-h.

References:

Pop, Laura;Lassalas, Pierrik;Bencze, Laszlo Csaba;Tosa, Monica Ioana;Nagy, Botond;Irimie, Florin Dan;Hoarau, Christophe [Tetrahedron Asymmetry,2012,vol. 23,# 6-7,p. 474 - 481] Location in patent:experimental part